Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 166
Filter
1.
Langmuir ; 40(41): 21499-21513, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39373461

ABSTRACT

Overuse of antibiotics can lead to increased bacterial resistance; therefore, there is a need to develop efficient nanomaterials for removing antibiotics from water. NiFe bimetallic hydroxide nanosheets doped with S-Cu were prepared on diatomite (S-CuNiFe LDH@diatomite) by using a two-step hydrothermal method. The surface of CuNiFe LDH@DE has a layered structure with an increased specific surface area and pore volume. The average pore size of S-CuNiFe LDH@De increases from 13.3 to 24.7 nm, and a more stereoscopic channel structure is obtained. Tetracycline removal experiments were performed on CuNiFe LDH@De and S-CuNiFe LDH@De. It was found that CuNiFe LDH@De had excellent photocatalytic performance and S-CuNiFe LDH@De had excellent adsorption performance. After CuNiFe LDH@De had been in contact with tetracycline (TC) for 2 h, the TC removal rate reached 95.6%. After S-CuNiFe LDH@De had been in contact with TC for 1 h, the adsorption capacity of TC was 145.5 mg/g. The pseudo-first-order kinetics and Sips isotherm model can be used to describe the adsorption process more accurately. The response surface method was used to optimize the adsorption conditions. According to the optimized conditions, a better adsorption performance of 166.9 mg/g was obtained. The two prepared materials showed good performance in the removal of tetracycline. This study provides a way to synthesize low-cost adsorbents and photocatalysts, which has value in the treatment of TC wastewater.


Subject(s)
Copper , Diatomaceous Earth , Surface Properties , Tetracycline , Tetracycline/chemistry , Copper/chemistry , Diatomaceous Earth/chemistry , Adsorption , Nickel/chemistry , Hydroxides/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Anti-Bacterial Agents/chemistry
2.
J Gastrointest Oncol ; 15(4): 1545-1555, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39279933

ABSTRACT

Background: Tumor budding (TB) has been shown to be a poor prognostic indicator after colorectal cancer (CRC) surgery. The aim of the present study is to evaluate the predictive role of morphological features (e.g., the number, structure, and location of tumor buds, and their reaction with the extracellular mesenchyme) in postoperative adjuvant chemotherapy in surgically resectable stage II CRC. Methods: Between 2016 and 2019, 336 patients with stage II CRC who underwent radical surgery were enrolled in this study. TB status was determined according to the criteria adopted at the 2016 International Tumor Budding Consensus Conference (ITBCC). We retrospectively recorded all the clinical and pathological data and assessed the effect of different types of TB status on patients' recurrence-free survival (RFS) and overall survival (OS). Results: Of the 336 patients, 173, 88, and 75 were budding grade 1 (BD1), BD2, and BD3, respectively. The 5-year RFS rates were 84.6%, 81.2%, and 68.0% (P=0.01), and the 5-year OS rates were 91.0%, 83.3%, and 76.2% (P=0.007) in BD1, BD2, and BD3, respectively. TB grade was strongly associated with vascular invasion status and mucinous adenocarcinoma, and BD3 was detected in 51.7% of patients with positive vascular invasion. The multivariate analysis showed that only age, perineural invasion, and TB grade [BD2 vs. BD1, hazard ratio (HR) =1.468, 95% confidence interval (CI): 0.703-3.063, P=0.30; BD3 vs. BD1, HR =2.310, 95% CI: 1.154-4.625, P=0.01] had an independent effect on RFS. In addition, the Kaplan-Meier curve analysis showed that BD3 patients had the worst RFS (P=0.01). The OS of the adjuvant chemotherapy group was significantly improved compared to that of the surgery-only group in the BD1/2 patients (HR =0.278, 95% CI: 0.114-0.676, P=0.005) but not in the BD3 patients with significant interaction (Pinteraction=0.03). Conclusions: Our results indicate that TB could play a subsidiary role in selecting stage II CRC patients who could achieve a favorable prognosis with chemotherapy.

3.
Stem Cell Res Ther ; 15(1): 299, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39267160

ABSTRACT

BACKGROUND: The established association between Alzheimer's disease (AD) and compromised neural regeneration is well-documented. In addition to the mitigation of apoptosis in neural stem cells (NSCs), the induction of neurogenesis has been proposed as a promising therapeutic strategy for AD. Our previous research has demonstrated the effective inhibition of NSC injury induced by microglial activation through the repression of oxidative stress and mitochondrial dysfunction by Sirtuin 3 (SIRT3). Nonetheless, the precise role of SIRT3 in neurogenesis remains incompletely understood. METHODS: In vivo, SIRT3 overexpression adenovirus was firstly injected by brain stereotaxic localization to affect the hippocampal SIRT3 expression in APP/PS1 mice, and then behavioral experiments were performed to investigate the cognitive improvement of SIRT3 in APP/PS1 mice, as well as neurogenic changes in hippocampal region by immunohistochemistry and immunofluorescence. In vitro, under the transwell co-culture condition of microglia and neural stem cells, the mechanism of SIRT3 improving neurogenesis of neural stem cells through DVL/GSK3/ISL1 axis was investigated by immunoblotting, immunofluorescence and other experimental methods. RESULTS: Our findings indicate that the overexpression of SIRT3 in APP/PS1 mice led to enhanced cognitive function and increased neurogenesis. Additionally, SIRT3 was observed to promote the differentiation of NSCs into neurons during retinoic acid (RA)-induced NSC differentiation in vitro, suggesting a potential role in neurogenesis. Furthermore, we observed the activation of the Wnt/ß-catenin signaling pathway during this process, with Glycogen Synthase Kinase-3a (GSK3a) primarily governing NSC proliferation and GSK3ß predominantly regulating NSC differentiation. Moreover, the outcomes of our study demonstrate that SIRT3 exerts a protective effect against microglia-induced apoptosis in neural stem cells through its interaction with DVLs. CONCLUSIONS: Our results show that SIRT3 overexpressing APP/PS1 mice have improved cognition and neurogenesis, as well as improved neurogenesis of NSC in microglia and NSC transwell co-culture conditions through the DVL/GSK3/ISL1 axis.


Subject(s)
Alzheimer Disease , Neural Stem Cells , Neurogenesis , Signal Transduction , Sirtuin 3 , Animals , Sirtuin 3/metabolism , Sirtuin 3/genetics , Mice , Alzheimer Disease/metabolism , Alzheimer Disease/therapy , Alzheimer Disease/genetics , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Glycogen Synthase Kinase 3/metabolism , Dishevelled Proteins/metabolism , Dishevelled Proteins/genetics , Mice, Transgenic , Microglia/metabolism , Cell Differentiation , Hippocampus/metabolism
4.
Nat Commun ; 15(1): 7272, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179532

ABSTRACT

RNAs are often modified to invoke new activities. While many modifications are limited in frequency, restricted to non-coding RNAs, or present only in select organisms, 5-methylcytidine (m5C) is abundant across diverse RNAs and fitness-relevant across Domains of life, but the synthesis and impacts of m5C have yet to be fully investigated. Here, we map m5C in the model hyperthermophile, Thermococcus kodakarensis. We demonstrate that m5C is ~25x more abundant in T. kodakarensis than human cells, and the m5C epitranscriptome includes ~10% of unique transcripts. T. kodakarensis rRNAs harbor tenfold more m5C compared to Eukarya or Bacteria. We identify at least five RNA m5C methyltransferases (R5CMTs), and strains deleted for individual R5CMTs lack site-specific m5C modifications that limit hyperthermophilic growth. We show that m5C is likely generated through partial redundancy in target sites among R5CMTs. The complexity of the m5C epitranscriptome in T. kodakarensis argues that m5C supports life in the extremes.


Subject(s)
Cytidine , Methyltransferases , Thermococcus , Transcriptome , Thermococcus/genetics , Thermococcus/metabolism , Thermococcus/enzymology , Methyltransferases/metabolism , Methyltransferases/genetics , Cytidine/metabolism , Cytidine/analogs & derivatives , Cytidine/genetics , Humans , RNA, Archaeal/genetics , RNA, Archaeal/metabolism , Archaeal Proteins/metabolism , Archaeal Proteins/genetics , RNA, Ribosomal/metabolism , RNA, Ribosomal/genetics
5.
Cancer Invest ; 42(6): 527-537, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965994

ABSTRACT

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Rectal Neoplasms/immunology , Male , Female , Middle Aged , Neoadjuvant Therapy/methods , Aged , Chemoembolization, Therapeutic/methods , Prognosis , Treatment Outcome , Adult , Chemoradiotherapy/methods
6.
Sci Rep ; 14(1): 15799, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982152

ABSTRACT

The technique of matrix acidification or acid fracturing is commonly utilized to establish communication with natural fractures during reservoir reconstruction. However, this process often encounters limitations due to filtration, which restricts the expansion of the primary acid-etching fracture. To address this issue, a computational model has been developed to simulate the expansion of an acid-etching wormhole by considering various factors such as formation process, injection duration, pressure build-up, and time-varying acid percolation rate. By analyzing the pumping displacement of acid-etching wormholes, this model provides valuable insights into the time-dependent quantities of acid percolation. It has been revealed that the filtration rate of acid-etching wormholes is strongly influenced by pumping displacement, viscosity, and concentration of the acid fluid used in stimulation as well as physical properties of the reservoir itself. Notably, viscosity plays a significant role in determining the effectiveness of acid fracturing especially in low-viscosity conditions. Acid concentration within 15% to 20% exhibits maximum impact on successful acid fracturing while concentrations below 15% or above 20% show no obvious effect. Furthermore, it was found that pumping displacement has a major influence on effective fracturing. However, beyond a certain threshold (> 5.0 m3/min), increased pumping displacement leads to slower etching distance for acids used in construction purposes. The simulation also provides real-time distribution analysis for acidity levels within eroded fractures during matrix-acidification processes and quantifies extent of chemical reactions between acids and rocks within these fractures thereby facilitating optimization efforts for design parameters related to matrix-acidification.

7.
Eur J Surg Oncol ; 50(9): 108527, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38968857

ABSTRACT

OBJECTIVE: To explore the different treatment modalities for esophageal gastrointestinal stromal tumors (E-GIST) and their respective applicability and clinical outcomes. METHODS: This is a retrospective study in which consecutive patients diagnosed with E-GIST at our hospital from January 2017 to August 2023 were included. The clinical characteristics of all the patients as well as long-term quality of life were recorded and analyzed. RESULTS: A total of 23 (12 males, 11 females) E-GIST patients with a mean age of 56.7 ± 12.0 years were included in this study. Common symptoms, including upper abdominal pain, acid reflux, and heartburn, accounted for over 60 % of cases. Fifteen patients underwent endoscopic resection, five patients underwent surgical resection, two patients underwent surgical resection after receiving preoperative imatinib therapy, and one patient received conservative management. CONCLUSION: Different treatment strategies may be applied to the patients with E-GIST depending on the their clinical features. Our study provides insights into precise treatment for different patients. However, due to the rarity of the disease, it is challenging to collect a large sample size from a single center, necessitating more multicenter prospective large-scale studies.


Subject(s)
Esophageal Neoplasms , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Humans , Male , Middle Aged , Female , Gastrointestinal Stromal Tumors/therapy , Gastrointestinal Stromal Tumors/surgery , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Retrospective Studies , Imatinib Mesylate/therapeutic use , Aged , Quality of Life , Antineoplastic Agents/therapeutic use , Adult , Heartburn/etiology , Abdominal Pain/etiology , Gastroesophageal Reflux/therapy , Esophagectomy/methods , Conservative Treatment/methods
8.
Org Lett ; 26(24): 5074-5081, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38857312

ABSTRACT

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

9.
Dig Liver Dis ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38744556

ABSTRACT

OBJECTIVE: The primary purpose of the study was to explore the clinical efficacy of the novel snare assisted endoscopic resection of extraluminal growing gastric gastrointestinal stromal tumors (gastric GISTs) using external traction, and the secondary purpose was to compare the novel snare assisted endoscopic resection of extraluminal GISTs with the standard laparoscopic procedure. METHODS: We retrospectively analyzed the patients who underwent novel external traction assisted endoscopic resection or laparoscopic resection for their extraluminal gastric GIST ≤5 cm in diameter. RESULTS: A total of 111 patients (27 in the endoscopic group and 84 in the laparoscopic group) were included in this study. There was no significant difference in tumor diameter and complication rate between the two groups. The overall procedure time was slightly higher in the endoscopic group compared to the laparoscopic group (P = 0.034). However, postoperative hospitalization time (P < 0.001) and postoperative fasting time (P = 0.005) were shorter in the endoscopic group compared to the laparoscopic group. CONCLUSION: Snare external traction-assisted endoscopic resection of extraluminal growing gastric GISTs is safe and effective, and it provides a new adjunctive method for endoscopic resection of GIST.

10.
Int J Mol Sci ; 25(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674153

ABSTRACT

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.


Subject(s)
Acute Lung Injury , Lipopolysaccharides , Serine Proteinase Inhibitors , Animals , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Mice , Serine Proteinase Inhibitors/pharmacology , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , NF-kappa B/metabolism , Male , Leukocyte Elastase/metabolism , Humans , Signal Transduction/drug effects , Recombinant Fusion Proteins/pharmacology , Disease Models, Animal
11.
Surg Endosc ; 38(6): 3329-3336, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38689159

ABSTRACT

OBJECTIVE: This study aims to investigate the efficacy and safety of snare traction-assisted endoscopic submucosal dissection (ESD) for the management of circumferential superficial esophageal cancer. METHODS: A total of 68 patients who underwent ESD for circumferential superficial esophageal cancer were included in this study. All the patients were divided into two groups based on whether the snare traction was used or not; the snare traction group (S-ESD, group n = 35) and the control group (C-ESD, group n = 33). RESULTS: There was no significant difference in the size of the resected area between the groups [21.98 (18.30, 27.00) cm2 vs 24.00 (15.28, 30.72) cm2, P = 0.976]. The snare traction group had a shorter dissection time [92.00 (74.00, 121.00) min vs 110.00 (92.50, 137.00) min, P = 0.017] and a faster resection speed [0.28 ± 0.13 cm2/min vs 0.22 ± 0.11cm2/min, P = 0.040] compared to the control group. There were no statistically significant differences between the two groups in terms of hospital stay, cost, en bloc resection rate, R0 resection rate, curative resection rate, bleeding rate, perforation rate, stricture rate, and recurrence rate (P > 0.05). CONCLUSION: Snare traction-assisted ESD is a safe and efficient approach for the treatment of circumferential superficial esophageal cancer. Its advantages includes shorter procedure so the anesthesia requirement, clear operative filed view, improved mucosal dissection efficiency, simple, and easily accessible equipment.


Subject(s)
Endoscopic Mucosal Resection , Esophageal Neoplasms , Humans , Endoscopic Mucosal Resection/methods , Endoscopic Mucosal Resection/instrumentation , Endoscopic Mucosal Resection/adverse effects , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Male , Female , Middle Aged , Aged , Treatment Outcome , Traction/methods , Retrospective Studies , Operative Time , Esophagoscopy/methods
12.
Langmuir ; 40(16): 8427-8439, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38607689

ABSTRACT

This work aims to enhance the adsorption performance of Laponite @diatomite for organic pollutants by modifying it with cetyltrimethylammonium bromide (CTAB). The microstructure and morphology of the CTAB-modified Laponite @diatomite material were characterized using SEM, XRD, FTIR, BET, and TG. Furthermore, the influences of key parameters, containing pH, adsorbent dosage, reaction time, and reaction temperature, on the adsorption process were investigated. The kinetics, thermodynamics, and isotherm models of the adsorption process were analyzed. Finally, potential adsorption mechanisms were given based on the characterization. The research findings indicate that CTAB-La@D exhibits good adsorption performance toward Congo red (CR) over a broad pH range. The maximum adsorption capacity of CR was 451.1 mg/g under the optimum conditions (dosage = 10 mg, contact time = 240 min, initial CR concentration = 100 mg/L, temperature = 25 °C, and pH = 7). The adsorption process conformed to the pseudo-second-order kinetic model, and the adsorption isotherms indicated that the adsorption process of CR was more in line with the Langmuir model, and it was physical adsorption. Thermodynamic analysis illustrates that the adsorption process is exothermic and spontaneous. Additionally, the mechanisms of electrostatic adsorption and hydrophobic effect adsorption of CR were investigated through XPS and FTIR analysis. This work provides an effective pathway for designing high-performance adsorbents for the removal of organic dye, and the synthesized materials hold great capability for practical utilization in the treatment of wastewater.

13.
Dig Dis Sci ; 69(5): 1755-1761, 2024 May.
Article in English | MEDLINE | ID: mdl-38483780

ABSTRACT

OBJECTIVE: To investigate the safety and prognosis of enbloc or piecemeal removal after enbloc resection of a gastric GIST by comparing the clinical data of endoscopic en block resection and piecemeal removal (EP) and en block resection and complete removal (EC) of gastric GISTs. METHODS: A total of 111 (43 endoscopic piecemeal, and 68 complete removal) patients with gastric GIST's ≥ 2 cm in diameter who underwent endoscopic therapy from January 2016 to June 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. In all cases, it was ensured that the tumor was intact during the resection, however, it was divided into EP group and EC group based on whether the tumor was completely removed or was cut into pieces which were then removed. The patients' recurrence-free survival rate and recurrence-free survival (RFS) were recorded. RESULTS: There was no statistically significant difference in RFS rates between the two groups (P = 0.197). The EP group had relatively high patient age, tumor diameter, risk classification, and operation time. However, there was no statistically significant difference in the number of nuclear fission images, postoperative hospitalization time, postoperative fasting time, complication rate and complication grading between the two groups (P > 0.05). CONCLUSION: Endoscopic piecemeal removal after en block resection of gastric GIST is safe and effective and achieves similar clinical outcomes as complete removal after en block resection.


Subject(s)
Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Female , Male , Middle Aged , Retrospective Studies , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Adult , Treatment Outcome , Gastroscopy/methods
14.
Org Lett ; 26(15): 3014-3019, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38547326

ABSTRACT

The radical relay provides an effective paradigm for intermolecular assembly to achieve functionalization across remote chemical bonds. Herein, we report the first radical relay 1,3-carbocarbonylation of α-carbonyl alkyl bromides across two separate C═C bonds. The reaction is highly chemo- and regioselective, with two C(sp3)-C(sp3) bonds and one C═O bond formed in a single orchestrated operation. In addition, the synthesis method under mild conditions and using inexpensive copper as the catalyst allows facile access to structurally diverse 1,3-carbocarbonylation products. The plausible mechanism is investigated through a series of control experiments, including radical trapping, radical clock experiments, critical intermediate trapping, and 18O labeling experiment.

15.
Eur J Surg Oncol ; 50(4): 108242, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38460248

ABSTRACT

BACKGROUND: Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified. METHODS: The comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results. RESULTS: The top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-ß and TP53 pathways were significantly associated with worse DFS. CONCLUSIONS: Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-ß and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Prognosis , Retrospective Studies , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Chemoradiotherapy , Rectal Neoplasms/genetics , Rectal Neoplasms/therapy , Mutation , Neoplasm Staging , Treatment Outcome , Tumor Suppressor Protein p53/genetics
17.
Mol Cell ; 84(5): 854-866.e7, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38402612

ABSTRACT

Deaminases have important uses in modification detection and genome editing. However, the range of applications is limited by the small number of characterized enzymes. To expand the toolkit of deaminases, we developed an in vitro approach that bypasses a major hurdle with their toxicity in cells. We assayed 175 putative cytosine deaminases on a variety of substrates and found a broad range of activity on double- and single-stranded DNA in various sequence contexts, including CpG-specific deaminases and enzymes without sequence preference. We also characterized enzyme selectivity across six DNA modifications and reported enzymes that do not deaminate modified cytosines. The detailed analysis of diverse deaminases opens new avenues for biotechnological and medical applications. As a demonstration, we developed SEM-seq, a non-destructive single-enzyme methylation sequencing method using a modification-sensitive double-stranded DNA deaminase. The streamlined protocol enables accurate, base-resolution methylome mapping of scarce biological material, including cell-free DNA and 10 pg input DNA.


Subject(s)
Cytosine Deaminase , Epigenome , DNA/genetics , Cytosine , DNA, Single-Stranded/genetics , Cytidine Deaminase/genetics
18.
Am J Clin Oncol ; 47(3): 115-121, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37981702

ABSTRACT

BACKGROUND: Concurrent chemoradiotherapy based on hyperfractionated accelerated radiotherapy (HART) is the first-line recommended regimen for the treatment of small-cell lung cancer (SCLC). However, Stereotactic Body Radiotherapy (SBRT) is also regarded as an effective treatment for limited-stage (LS) SCLC, and the efficacy and safety of HART versus SBRT stay controversial. METHODS: In this study, 188 LS-SCLC patients were retrospectively divided into two groups receiving chemotherapy combined with either HART or SBRT. In HART group, patients received 4500 cGy in 30 fractions, administered twice daily for 3 weeks. Whereas in the SBRT group, a total radiation dose of 4000-4500 cGy was delivered in 10 fractions over 2 weeks. Thirty-three pairs of patients were finally included for next analysis. RESULTS: The estimated objective response rates were 63.6 % (21/33) and 78.8 % (26/33) in HART group and SBRT group, respectively (P = 0.269). Furthermore, there was no significant difference between HART and SBRT groups in overall survival (26 months vs. 29 months, P = 0.362) and progression free survival (11 months vs. 15 months, P = 0.223). As for the adverse events, toxicity of both groups is similar and slight that no grade 4 event was observed. Grade 3 pneumonitis cases were all occurred in the HART group (9.1%, 3/33, P = 0.238), and grade 3 esophagitis cases were all occurred in the SBRT group (6.1%, 2/33, P = 0.492). CONCLUSION: Compared with HART, SBRT could be another effective treatment with satisfactory safety for the concurrent chemoradiotherapy in patients with LS-SCLC.


Subject(s)
Lung Neoplasms , Radiosurgery , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/radiotherapy , Small Cell Lung Carcinoma/drug therapy , Lung Neoplasms/therapy , Radiosurgery/adverse effects , Matched-Pair Analysis , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dose Fractionation, Radiation
19.
Life Sci Alliance ; 7(2)2024 02.
Article in English | MEDLINE | ID: mdl-38030223

ABSTRACT

RNA modifications, such as methylation, can be detected with Oxford Nanopore Technologies direct RNA sequencing. One commonly used tool for detecting 5-methylcytosine (m5C) modifications is Tombo, which uses an "Alternative Model" to detect putative modifications from a single sample. We examined direct RNA sequencing data from diverse taxa including viruses, bacteria, fungi, and animals. The algorithm consistently identified a m5C at the central position of a GCU motif. However, it also identified a m5C in the same motif in fully unmodified in vitro transcribed RNA, suggesting that this is a frequent false prediction. In the absence of further validation, several published predictions of m5C in a GCU context should be reconsidered, including those from human coronavirus and human cerebral organoid samples.


Subject(s)
Algorithms , RNA , Animals , Humans , RNA/genetics , Methylation , Sequence Analysis, RNA
20.
BMC Psychiatry ; 23(1): 907, 2023 12 05.
Article in English | MEDLINE | ID: mdl-38053101

ABSTRACT

BACKGROUND: Patients' attitudes toward medication have been shown to be a predictor of nonadherence to antipsychotic treatment. However, most previous studies that explored this relationship used a cross-sectional design. It is important to explore the association of attitudes toward drugs with discontinuation at different time points during antipsychotic treatment. In this study, we investigated the association of attitudes toward drugs (measured by the Drug Attitude Inventory (DAI-10)) with adherence at seven time points (baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks, and 52 weeks) during 1 year of treatment. Factors that were potentially associated with attitudes toward drugs at the time point of interest were also studied. METHODS: Demographic characteristics, psychopathology, social functioning, and attitudes toward drugs (measured by the DAI-10) were collected at baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks and 52 weeks. The association of attitudes toward drugs (measured by DAI-10) with adherence at the seven time points was calculated using the Mann‒Whitney U test. The optimal cutoff point for the DAI-10 was then determined using receiver operating characteristic (ROC) analysis. Cox regression analysis was conducted to further investigate the association of DAI-10 scores with discontinuation, controlling for potential confounding variables. We used multiple regression analysis to identify the factors associated with DAI-10 scores. RESULTS: Among the six time points, only baseline DAI-10 total scores were significantly different between the completed and discontinued groups (p = 0.004). Female sex and a baseline DAI-10 total score greater than - 1 were found to be independent protective factors against discontinuation of antipsychotic drug treatments during the 1-year follow-up. At baseline, the severity of the disease (CGI-s) and insight regarding the disease were shown to be associated with DAI-10 total scores. CONCLUSION: Attitudes toward antipsychotic drugs at baseline were shown to play a crucial role in predicting treatment discontinuation. TRIAL REGISTRATION: The data were collected from a clinical trial and the clinical trials.gov ID of the study is NCT01057849.


Subject(s)
Antipsychotic Agents , Schizophrenia , Humans , Female , Schizophrenia/drug therapy , Antipsychotic Agents/therapeutic use , Prospective Studies , Cross-Sectional Studies , Medication Adherence
SELECTION OF CITATIONS
SEARCH DETAIL